Document Detail


Effect of estrogen on neprilysin expression in uterus and kidney of Sprague-Dawley normotensive and heterozygous (mRen2)27-transgenic hypertensive rats.
MedLine Citation:
PMID:  16890325     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The present study was designed to determine whether estrogen modulates the angiotensin processing enzymes in membrane homogenates obtained from uterus and kidney cortex and medulla of Sprague-Dawley (SD) and heterozygous (mRen2)27-transgenic hypertensive (Tg(+)) female rats treated with or without 17beta-estradiol (E2). We evaluated estrogen's influence on neprilysin (NEP), an endopeptidase that forms angiotensin-(1-7) [Ang-(1-7)] and on aminopeptidase (AMP), which degrades Ang-(1-7). Renal tissue from normotensive and hypertensive male rats was also evaluated. E2 up-regulated NEP mRNA in the uterus of both SD and Tg(+) and this was associated with increased NEP activity in the uterus of SD (0.31+/-0.03 nmol/min/mg versus 0.18+/-0.04 nmol/min/mg of protein, p<0.05) and Tg(+) (0.26+/-0.04 nmol/min/mg versus 0.13+/-0.02 nmol/min/mg of protein, p<0.05) female). E2 had no significant effect on NEP activity in cortex and medulla of hypertensive and normotensive female. In female animals, cortical NEP activity is two-fold higher than medullary; in males there is a four-fold higher cortical NEP activity as compared to medulla. In male animals, medullary NEP was significantly lower than females with or without E2 treatment; no gender specific effect was found in cortex. E2 treatment also caused a two-fold increase in AMP activity in the uterus and 1.6-fold decrease in kidney cortex of SD and Tg(+) female (p<0.05). Our studies indicate that NEP may be a primary candidate for increased Ang-(1-7) processing in the uterus with estrogen treatment; kidney NEP, on the other hand, showed no modulation by estrogen, suggesting that down regulation of other processing enzymes, like AMP and ACE, may come into play in the kidney with estrogen replacement. In addition, these studies showed that there is tissue-specific regulation of NEP with estrogen treatment that is strain independent.
Authors:
L A A Neves; M C Chappell; C M Ferrario; P E Gallagher; D Ganten; K B Brosnihan
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-08-04
Journal Detail:
Title:  Peptides     Volume:  27     ISSN:  0196-9781     ISO Abbreviation:  Peptides     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-10-23     Completed Date:  2007-05-10     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  8008690     Medline TA:  Peptides     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2912-8     Citation Subset:  IM    
Affiliation:
The Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1932, USA.
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MeSH Terms
Descriptor/Qualifier:
Aminopeptidases / metabolism
Animals
Animals, Genetically Modified
Blood Pressure / drug effects
Estrogens / pharmacology*
Female
Heterozygote
Hypertension / genetics,  physiopathology*
Kidney / drug effects,  enzymology,  metabolism*
Male
Neprilysin / genetics,  metabolism*
Ovariectomy
RNA, Messenger / metabolism
Rats
Rats, Sprague-Dawley
Reference Values
Renin / genetics*
Sex Characteristics
Uterus / drug effects,  metabolism*
Grant Support
ID/Acronym/Agency:
HL56973/HL/NHLBI NIH HHS; HL62489/HL/NHLBI NIH HHS; P01 HL58952/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Estrogens; 0/RNA, Messenger; 0/Ren2 protein, mouse; EC 3.4.11.-/Aminopeptidases; EC 3.4.23.15/Renin; EC 3.4.24.11/Neprilysin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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